Inspections, Compliance, Enforcement, and Criminal Investigations
International BioResources LLC 22-Jun-06
Department of Health and Human Services
Public Health Service
June 22, 2006
RETURN RECEIPT REQUESTED
Mr. Rodney Savoy
Chief Executive Officer
International BioResources, LLC.
1100 Camellia Boulevard, Suite 201
Lafayette, Louisiana 70508
Dear Mr. Savoy:
The Food and Drug Administration (FDA) conducted an inspection of your firm, International BioResources, LLC, located at 2520 Jacksboro Hwy, Ft. Worth, Texas, from April 25 through May 10, 2006. During the inspection, the FDA investigator documented violations of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) and Title 21, Code of Federal Regulations (21 CFR) Parts 600-680 . Listed below are certain serious violations that reveal problems with your firm's Good Manufacturing Practices (GMP). We did not list all of your firm's violations. These violations represent observations noted on the Form FDA-483 issued at the conclusion of the inspection.
1. Your firm failed to determine that donors for Source Plasma met suitability on the day of collection [21 CFR 640.63(a)].
Specifically, your firm discovered that ten donors had not been asked all of the sixteen medical history questions on the day of collection of Source Plasma. Although your firm discovered these deviations, nine out of the ten units of Source Plasma collected from these donors were shipped.
For example :
One donation occurred on March 18, 2005. The missing health questions were discovered on March 22, 2005 during a donor record review. However, when this error was discovered, the donor was not contacted and there was no notation that employees or management followed up with the medical questions when the donor returned on July 14, 2005. In addition, during some subsequent donation, an employee marked these questions as if the donor had answered the day of the donation. Your firm also documented that this unit of Source Plasma had been destroyed but all records indicate that the unit was shipped April 25, 2005.
The most recent donation where the medical history questions were not answered occurred on January 9, 2006. The missing medical health questions were discovered by your firm on January 10, 2006. Once again, the donor was not contacted. When the donor returned on January 12, 2006, a notation was made that the donor was counseled pertaining to the missing health questions and that no change or alternative answers were given . Records indicate this unit was shipped on February 13, 2006.
In addition to the employees not asking the medical health history questions during the donor screening for these nine units; the front supervisor, the quality associates, the center manager, and additional employees did not review the donor record adequately to discover that the medical history questions were not asked/answered as required by the Standard Operating Procedure (SOP), Donor Record Review.
Therefore, because your firm failed to determine donor suitability on the day of collection, your firm did not ensure that these final products have the safety, purity, and potency that the products purport or are represented to possess.
2. Your firm did not review all records pertinent to the lot or unit before the release or distribution of a lot or unit of final product [21 CFR 606.100(c)].
Although your firm did create Internal Investigation Reports (IIR) for these nine units and discovered that the medical history questions were not answered for these donations, your firm released and shipped these nine units of Source Plasma for further manufacturing into licensed products.
3. Your firm does not have written standard operating procedures including all criteria to be followed to determine donor suitability, including acceptable medical history criteria [21 CFR 606.100(b)(1)].
Specifically, your firm does not have an SOP that has directions to follow when the donor medical history questions are not answered completely. For example, there are no directions to contact the donor as soon as this error is discovered. In addition, your firm's SOPs do not give any directions to the quality supervisors or other management to quarantine the product if the donor history questions are not answered.
4. Your firm did not follow standard operating procedures including all the steps to be followed in the collection of blood and blood components for further manufacturing [21 CFR 606.100(b)].
In ten separate donations, SOPs for donor records for the donation process and the donor screening job aid were not followed because the donor medical history questions were not asked for these ten donors. In addition, the SOP for the donor record review was not followed because in all the above cases, during the pre-donation review, the reviewer did not notice that the medical history questions had not been answered by the donor prior to beginning the plasma collection process.
5. Your firm did not have personnel who are adequately trained or experienced in the collection of blood and blood components to assure competent performance of the assigned functions and to ensure that the final product has the safety, purity, and potency that it purports or is represented to possess [21 CFR 606.20(b)].
The review of the IIRs revealed that five out of ten records stated that the employees would receive training or they had received remedial training. For example, one IIR stated that staff received retraining on 26 JAN 05 on proper donor record file (DRF) review. Missing health questions were addressed in this meeting . Another IIR generated on November 30, 2005, documented that a staff member received remedial instructions for concurrent documentation on November 11, 2005. In addition, the SOP for donor exception reports states that the IIR is closed by Quality Management after all the reassessments are complete. Although your firm documented that retraining of the staff was done, the training has not been effective for assessing donor suitability because the missing history questions continued to be a deviation.
6. Your firm failed to submit biological product deviation reports (BPDR) [21 CFR 606.171(b)]. Specifically, when all the medical history questions were not asked for these nine units of Source Plasma on the day of collection, your firm deviated from the current good manufacturing practices and applicable regulations that may affect the safety, purity, and potency of these products. In addition, your firm released and shipped these nine units of Source Plasma for further manufacturing. Furthermore, when our investigator made this discovery during this inspection, your firm did not recognize that these deviations had to be reported as BPDRs.
The above identification of violations is not intended to be an all-inclusive list of deficiencies at your facility . It is your responsibility to ensure that all Source Plasma produced for further manufacturing by your Source Plasma firm are in compliance with the Act and the cGMP regulations. You should take prompt action to correct these violations . Failure to correct these violations may result in administrative and/or regulatory action without further notice. Such action includes license suspension and /or revocation, seizure and/or injunction.
We received your May 16, 2006 and May 30, 2006 response to the FDA 483, Inspectional Observations that the FDA investigator issued at the conclusion of the most recent inspection of your firm. We have completed our review of your response and have determined that your response does not adequately and/or completely address all the violations that FDA documented at your firm. Our evaluation follows and is labeled to correspond to the items as they appeared in your response:
Item 1, a-i. Your response is incomplete to address the noted observation. You state that when your firm discovered that the medical history questions had not been answered, a full investigation took place that was documented on the Internal Investigation Report (IIR) but there is no documentation that the investigation determined that these products were safe, pure or potent and could be distributed . Furthermore, your firm did not complete the Product Investigation Report for a complete evaluation of these nine units until they were discovered by FDA during the current inspection . In your initial response dated May 16, 2006, you state that these deviations of missing medical history questions occurred under the previous manager and quality supervisor and that these persons are no longer in your employment as of January 2006. However, one unit of Source Plasma that had missing donor history questions was shipped February 13, 2006, under your new management that you state has the qualifications and experience to ensure full compliance with procedural requirements. In addition, you state that the Job Aid will be assessed by the CAPA committee for effectiveness but the Work Instruction memorandum (WIM) WIM 049, and the SOP for Donor Suitability Alert Flags will be implemented as soon as the staff training is complete. You do not state how the effectiveness of the training on these procedures will be assessed and what corrective action will take place if the training is not effective.
Item 2, a-i. Your response is incomplete. You state that because the IIR was completed and the corrective actions were appropriate, the center manager closed the IIR and no further records review was required prior to unit distribution. However, your evaluation of the safety and purity of the product was based on the donor's answers to the medical history questions when the donor returned to donate which varied in time from three days to approximately three months. Although a partial assessment of the safety and purity of the product can be evaluated by the testing of the product, the suitability of the donor to donate is to be determined the day of donation by the answers given to the medical history questions . In your initial response dated May 16, 2006, you do not state that documentation for the effectiveness of WIM 046 will be submitted.
In addition, you do not state what corrective actions or SOPs you will have in place if this review fails to discover any missing information for donor suitability that is required before the collection process takes place.
Item 3. Your response appears to be adequate. In addition, you continue to state that there was no impact to donor safety or product quality after you initiated a complete review of the health history responses to previous and subsequent donations and the results of viral testing markers for these products. In your initial response dated May 16, 2006, you also stated that there was no impact to donor safety or product quality on these units identified during the FDA inspection. However, the missing answers to the medical history questions can affect the quality of the product because the answers to several of the questions are directly related to a communicable disease or infection that could not be detected by the required testing of the Source Plasma units. Therefore, your impact analysis cannot definitely determine that there is no compromise in the safety, purity and potency of these implicated units.
Item 4 a, b. Your response appears to be adequate to address the noted observation . However, even though you state that the SOP for Center Exceptions Reporting provides directions for identifying, implementing corrective action, and preventive actions, your firm did not take the necessary corrective actions to prevent these products from being distributed. In addition, you have written the WIM 049 to supplement this SOP and state that all personnel will be trained prior to the date for implementation of the WIM 049. However, as stated in Item 1, you do not give a date for assessment of the effectiveness of the WIM 049 or what corrective actions will be taken if this WIM 049 is not effective.
Item 5 a, b. & Item 5 a, b,c. Your response appears to be adequate to address the noted observation . However, even though you state that all personnel have been re-trained to follow the SOPs, your new management continues to fail to do an adequate assessment of the training of the employees as observed during the current FDA inspection . In your initial response dated May 16, 2006, you state that the employees that were involved with the FDA 483 observations related to missing health questions and quality reviews are gone or have been fully recertified; however, your training of employees has not been effective as evidenced by the observations on the FDA 483.
Item 6. The response appears to be adequate.
Item 7. The response is incomplete. Again, your firm does not give any dates for reassessment of this training program and how the effectiveness will be measured . In your initial response dated May 16, 2006, you state that a Corporate Corrective and Preventive Action (CAPA) plan is being prepared to enhance quality systems and manufacturing controls at IBR facilities. However, your quality team had performed an audit of your firm and did not discover that these nine units had been shipped even though an IIR had been generated for the deviation of the missing answers to the medical history questions.
Performing a complete audit as a corrective action may determine the status of compliance with your firm's quality program, but unless the management of your firm and the training of your employees is sufficient to prevent the shipment of such units, deviations to the FDA regulations will continue to occur.
Item 8. The response appears to be adequate; however, a Biological Product Deviation Report (BPDR) has to be submitted to CBER when a deviation occurs that could effect the safety, purity, and potency of the product and the product has been distributed. The medical history questions were not answered for these nine units; therefore, the product does not meet all the criteria to determine that the product is safe, pure, and potent. In your initial response dated May 16, 2006, you state that BPDRs were submitted as a precautionary measure pending the completion of the incident reexamination ; however, your firm is required to report any biological deviation that has occurred that may effect the safety, purity, and potency of the product to the Center of Biological Evaluation and Research if the product is collected and distributed by your facility regardless of your firm's impact assessment.
In addition, on June 21, 2006, your firm had a teleconference with us to explain in more detail your written response.
We request that you notify this office in writing, within fifteen (15) working days of the receipt of this letter, of the specific steps you have taken to correct these violations, including examples of any documentation showing that corrections have been achieved. If you cannot complete all the corrections before you respond, please explain the reason for your delay and the date by which each item will be corrected and documented.
Please send your reply to the Food and Drug Administration, Attention: Carolyn A. Pinney, Compliance Officer, at the above letterhead address. If you have any questions regarding any issue in the letter, please contact Carolyn A. Pinney at (214) 253-5220.
Sylvia Y. Yetts for Michael A. Chappell